Biology subjects

Balbi, M.

Publications and source records attributed to Balbi, M..

5 recordsLinked to original sources

bioRxiv2026

Recipient-driven metabolic and epigenetic remodeling of donor hematopoietic cells after transplantation in Fanconi Anemia.

Background Haematopoietic cell transplantation (HCT) restores donor-derived haematopoiesis in Fanconi anaemia (FA) but leaves recipient stromal and other non-haematopoietic cells genetically uncorrected. We investigated to what extent the persistent FA recipient environment influences the metabolic, redox, inflammatory and epigenetic phenotype of donor-derived haematopoietic cells after HCT. Methods Peripheral blood and, when available, bone marrow samples were analysed from healthy donors, patients with FA before and after HCT, and severe aplastic anaemia (SAA) patients after HCT as transplant controls. Mitochondrial function, cellular energy status, oxidative damage, antioxidant responses and circulating cytokines were assessed. Healthy donor mononuclear cells were exposed to conditioned media from FANCA-deficient mesenchymal stromal cells or FA fibroblasts, with FANCA-corrected fibroblasts as controls. DNA methylation profiling, acute inflammatory stimulation and pharmacological targeting of inflammatory pathways or mitochondrial oxidative stress were also performed. Results Despite stable full donor chimerism, FA recipients retained a pro-inflammatory and pro-oxidative circulating environment after HCT that was not observed in SAA transplant controls. Donor-derived mononuclear cells exposed to this environment acquired a distinct dysfunctional phenotype characterized by impaired mitochondrial oxidative phosphorylation and energy homeostasis, compensatory antioxidant and stress-response activation, and persistent lipid and protein oxidation. These alterations remained detectable after 96 h of ex vivo culture, suggesting relatively stable cellular remodelling, and were accompanied by a DNA methylation profile that, although globally shifted toward the donor state, retained an intermediate FA-associated episignature. Mechanistically, conditioned media from FANCA-deficient stromal cells and FA fibroblasts reproduced mitochondrial and oxidative abnormalities in healthy donor cells, whereas FANCA-corrected fibroblasts did not. Pharmacological targeting of inflammatory pathways or mitochondrial oxidative stress improved energy homeostasis and reduced oxidative damage, supporting a contributory role for chronic inflammation and oxidative stress in the microenvironment-driven phenotype acquired by donor-derived cells. Conclusions HCT corrects FA haematopoiesis without fully normalising the recipient environment. Persistent exposure to the FA milieu promotes metabolic, redox, signalling and epigenetic remodelling of donor-derived haematopoietic cells after transplantation. These findings identify the recipient environment as a determinant of post-HCT cell biology and highlight chronic inflammation and oxidative stress as mechanisms contributing to donor-cell remodelling in FA.

cell biology↗

bioRxiv2025

Therapeutic efficacy of hiMSC-derived Extracellular Vesicles from Serum-containing and Xeno-free media for osteoarthritis treatment

BackgroundExtracellular vesicles derived from human induced mesenchymal stromal cells (hiEVs) constitute a promising cell-free therapeutic option for osteoarthritis. To allow translation to the clinic we evaluated the therapeutic effects of hiEVs for osteoarthritis treatment. Specifically, we assessed the efficacy of hiEVs collected from serum-containing and serum-free, PurStem (PS), media in an OA mice model. MethodshiEVs were administered with or without hydrogel via intra-articular (i.a.) injection in a destabilization of the medial meniscus (DMM) mouse model. Fluorescence imaging was used to monitor the retention of IR780-labeled hiEVs in the joint cavity. The therapeutic effects were evaluated by analyzing damage scores as well as catabolic and anabolic markers, including Mmp13 and Col2 expression, in joint tissues. ResultsFluorescence imaging confirmed that hiEVs remained localized at the injection site without systemic migration. HiEVs demonstrated significant protective effects against joint tissue degeneration in the DMM mouse OA model, as evidenced by reduced damage scores, decreased Mmp13 expression, and increased anabolic processes (Col2 expression). The hydrogel alone also exerted beneficial therapeutic effects, including reduced damage scores, increased Col2 expression, and reduced Mmp13 levels; however, these effects were notably smaller than those achieved with hiEV treatment while it was independent of the medium used for hiEV collection. ConclusionsTogether, our findings demonstrate that hiEVs from xeno-free conditions effectively prevent cartilage degradation and promote its repair. This paves the way for future clinical translation of hiEV-based therapies as a safe, scalable, and effective approach to treat osteoarthritis.

developmental biology↗

bioRxiv2025

miR-29a-3p and TGF-beta Axis in Fanconi Anemia: Mechanisms Driving Metabolic Dysfunction and Genome Stability

Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure and cancer susceptibility due to defective DNA double-strand break repair. However, FA cells are also characterized by mitochondrial dysfunction and redox imbalance. To identify a common factor among these alterations, we focused on miR-29a-3p, a microRNA involved in hematopoiesis. Our data show that miR-29a-3p is downregulated in lymphoblasts and fibroblasts mutated for the FANC-A gene, causing the overexpression of its target genes, FOXO3, SGK1, and IGF1, which results in PI3K/AKT pathway hyperactivation, altered mitochondrial metabolism and insufficient antioxidant response. Furthermore, miR-29a-3p downregulation appears associated with hyperactivation of the TGF-{beta} signal. However, restoring miR-29a-3p expression improves mitochondrial metabolism, oxidative stress response, and DNA damage repair by inhibiting the PI3K/AKT pathway and modulating TGF-{beta} signaling by a feedback mechanism. Based on these findings, miR-29a-3p appears as a promising molecular target to address several mechanisms based on FA pathogenesis.

cell biology↗

bioRxiv2019

Simulated neutral metacommunities support the habitat amount hypothesis

AO_SCPLOWBSTRACTC_SCPLOWThe Theory of Island Biogeography (TIB) promoted the idea that species richness within sites depends on site connectivity, i.e. its connection with surrounding potential sources of immigrants. TIB has been extended to a wide array of fragmented ecosystems, beyond archipelagoes, surfing on the analogy between habitat patches and islands and on the patch-matrix framework. However, patch connectivity often little contributes to explaining species richness in empirical studies. Before interpreting this trend as questioning the broad applicability of TIB principles, one first needs a clear identification of methods and contexts where strong effects of patch structural connectivity are likely to occur. Here, we use spatially explicit simulations of neutral metacommunities to show that patch connectivity effect on local species richness is maximized under a set of specific conditions: (i) patch delineation should be fine enough to ensure that no dispersal limitation occurs within patches, (ii) patch connectivity indices should be scaled according to target organisms dispersal distance and (iii) the habitat amount around sampled sites (within a distance adapted to organisms dispersal) should be highly variable. When those three criteria are met, the absence of an effect of connectivity on species richness should be interpreted as contradicting TIB hypotheses

ecology↗

bioRxiv2018

Mesoscale cortical calcium imaging reveals widespread synchronized infraslow activity during social touch in mice

We employ cortical mesoscale calcium-imaging to observe brain activity in two head-fixed mice in a staged social touch-like interaction. Using a rail system, mice are brought together to a distance where macrovibrissae of each mouse make contact. Cortical signals were recorded from both mice simultaneously before, during, and after the social contact period. When the mice were together, we observed bouts of mutual whisking and cross-mouse correlated cortical activity in the vibrissae cortex. This correlated activity was specific to individual interactions as the correlations fell in trial-shuffled mouse pairs. Whisk-related global GCAMP6s signals were greater in cagemate pairs during the together period. The effects of social interaction extend outside of regions associated with mutual touch and had global synchronizing effects on cortical activity. We present an open-source platform to investigate the neurobiology of social interaction by including mechanical drawings, protocols, and software necessary for others to extend this work.

neuroscience↗